Release of endothelial activation markers in lungs of patients with malaria-associated acute respiratory distress syndrome

Thao-Thy Pham, Chuchard Punsawad, Supattra Glaharn, Simon F De Meyer, Parnpen Viriyavejakul, Philippe E Van den Steen

Research output: Contribution to journalA1: Web of Science-articlepeer-review

Abstract

Background: Malaria-associated acute respiratory distress syndrome (MA-ARDS) is an understudied complication of malaria and is characterized by pulmonary inflammation and disruption of the alveolar-capillary membrane. Its pathogenesis remains poorly understood. Since endothelial activation plays an important role in other malarial complications, the expression of two endothelial activation markers, von Willebrand factor (VWF) and angiopoietin-2 (ANG-2), was investigated in the lungs of patients with MA-ARDS.

Methods: Post-mortem lung sections of Plasmodium falciparum-infected patients without alveolar oedema (NA), P. falciparum-infected patients with alveolar oedema (MA-ARDS), and uninfected people who died accidentally with no pathological changes to the lungs (CON) were immunohistochemically stained for VWF and ANG-2, and were evaluated with semi-quantitative analysis.

Results: Alveolar oedematous VWF and ANG-2 and intravascular VWF staining were significantly increased in patients with MA-ARDS versus infected and uninfected control groups. The levels of VWF in the alveolar septa and endothelial lining of large blood vessels of patients with MA-ARDS was significantly decreased compared to controls. ANG-2 expression was increased in the alveolar septa of malaria patients without alveolar oedema versus control patients, while ANG-2+ leukocytes were increased in the alveoli in both infected patient groups.

Conclusions: This study documents a high level of VWF and ANG-2, two endothelial activation markers in the oedematous alveoli of post-mortem lung sections of Thai patients with MA-ARDS. Decreased detection of VWF in the endothelial lining of blood vessels, in parallel with an increased presence of intravascular VWF staining suggests marked endothelial activation and Weibel-Palade body release in the lungs of patients with MA-ARDS.

Original languageEnglish
Article number395
JournalMalaria Journal
Volume18
Issue number1
ISSN1475-2875
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • Adult
  • Angiopoietin-2/metabolism
  • Female
  • Humans
  • Lung/parasitology
  • Malaria/complications
  • Male
  • Respiratory Distress Syndrome/diagnosis
  • Young Adult
  • von Willebrand Factor/metabolism

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